Stem cells are capable of self-renewal and can differentiate into specialized cell types. Pluripotent stem cells, such as those found in the embryo, retain the potential to differentiate into any cell type of the organism. The ability to culture pluripotent stem cells has created enormous research and therapeutic potential. For example, directing the differentiation of stem cells to grow desired cell types, tissues, and organs could provide an unprecedented tool in the clinic by providing a means for transplantation and/or repair of damaged tissues and organs, such as cardiac muscle. Directed differentiation of stem cells would also provide an inexhaustible supply of cells for drug screens and for the exploration of fundamental questions of basic research. The advent of induced pluripotent stem cell technology, which facilitates the derivation of pluripotent stem cells from differentiated adult cells, further opened the door for the exploitation of patient-derived pluripotent stem cells to achieve personalized medicine.
Cardiomyocytes are the muscle cells of the heart and can be produced in vitro by directing the differentiation of pluripotent stem cells. Cardiomyocytes produced in culture exhibit features in common with those isolated from heart tissue. Namely, cardiomyocytes in culture begin to spontaneously beat and do so in a synchronized manner. The ability to produce beating cardiomyocytes in culture has far reaching implications for the clinic, including the repair of damage caused by myocardial infarction.
Secreted Wnt glycoproteins form a family of signaling molecules that trigger the highly conserved Wnt signaling pathway, which regulates numerous cell-to-cell interactions during embryogenesis and throughout adult life. The Wnt signaling pathway controls several aspects of cellular behavior, including cell differentiation, cell growth, cell proliferation, cell survival, morphogenesis, organogenesis, and tissue patterning. Controlled timing and levels of Wnt signaling are crucial for several facets of proper heart development, including the differentiation of cardiomyocytes and cardiomyocyte progenitors. As such, the directed differentiation of cardiomyocytes from pluripotent stem cells in vitro can be achieved by temporal control of the Wnt signaling pathway.
The production of cardiomyocytes produced from pluripotent stem cells for use in therapy and/or research will benefit from reduced cost, increased efficiency, increased reproducibility, increased flexibility (successful implementation using multiple different stem cell lines), increased scalability, and increased availability of essential components. The present invention addresses these needs.
Publications
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